Toxicity effects of disinfection byproduct chloroacetic acid to Microcystis aeruginosa: Cytotoxicity and mechanisms.

Chlorine-based disinfectants are widely used for disinfection in wastewater treatment. The mechanism of the effects of chlorinated disinfection by-products on cyanobacteria was unclear. Herein, the physiological effects of chloroacetic acid (CAA) on Microcystis aeruginosa (M. aeruginosa), including acute toxicity, oxidative stress, apoptosis, production of microcystin-LR (MC-LR), and the microcystin transportation-related gene mcyH transcript abundance have been investigated. CAA exposure resulted in a significant change in the cell ultrastructure, including thylakoid damage, disappearance of nucleoid, production of gas vacuoles, increase in starch granule, accumulation of lipid droplets, and disruption of cytoplasm membranes. Meanwhile, the apoptosis rate of M. aeruginosa increased with CAA concentration. The production of MC-LR was affected by CAA, and the transcript abundance of mcyH decreased. Our results suggested that CAA poses acute toxicity to M. aeruginosa, and it could cause oxidative damage, stimulate MC-LR production, and damage cell ultrastructure. This study may provide information about the minimum concentration of CAA in the water environment, which is safe for aquatic organisms, especially during the global coronavirus disease 2019 pandemic period.

Mutation scanning of BRAF, NRAS, KIT, and GNAQ/GNA11 in oral mucosal melanoma: a study of 57 cases.

BACKGROUND: Recent advances in novel targeted therapies have created the need for molecular characterization of cancer to allow accurate personalized treatments. In this study, our aim was to investigate the incidence of activating mutations of oncogenes BRAF, NRAS, KIT, and GNAQ/GNA11 in oral mucosal melanoma. METHODS: We analyzed a cohort of 57 oral mucosal melanoma samples, including 27 frozen samples and 30 formalin-fixed paraffin-embedded samples. The tumors were screened for hotspot mutations of BRAF (exon 15), NRAS (exons 2 and 3), KIT (exons 9, 11, 13, and 17), and GNAQ/GNA11 (exon 5) by high-resolution melting and direct sequencing. RESULTS: In oral mucosal melanoma, 7.0% of tumors harbored KIT mutations and 3.5% harbored BRAF mutations, while classic BRAF V600E mutation was not detected. We found no mutations of NRAS or GNAQ/GNA11 in oral mucosal melanoma. CONCLUSION: We demonstrated that driver mutations are rare in mutational hotspots of BRAF, NRAS, KIT, and GNAQ/GNA11 in oral mucosal melanoma. The majority of patients will not benefit from KIT and BRAF inhibitors.

Primary Malignant Melanoma of the Lip: A Report of 48 Cases.

PURPOSE: Lip melanoma (LM) is a rare malignant tumor and well-established treatment protocols for it are in short supply. The objective of this study was to evaluate the outcome of treatment modalities and explore the prognostic factors. PATIENTS AND METHODS: A retrospective chart review was performed on 48 patients with primary LM treated in the authors' hospital from January 1992 to November 2013. The clinical characteristics and treatment modalities were identified and correlated with the outcomes. RESULTS: The 5-year overall survival (OS) rate was 56.1%, and the rate of cervical lymph node (CLN) metastasis was 46% (22 of 48). A tumor of at least 4 cm (P = .001), nodular types (P = .003), and CLN (P < .0001) were independent prognostic factors for OS. Twenty-five patients died during follow-up, mainly from to neck recurrence (14 of 25). Chemotherapy significantly improved the 5-year OS rate in patients with stage IV LM (P = .03), but not in those with stage III (P = .8). CONCLUSIONS: LM has a lower CLN and distant metastasis rate and a better prognosis than other oral mucosal melanomas. A long history of melanin pigmentation is a dangerous sign for all patients, and smoking seems to be associated with LM in male patients. Tumor size (≥4 cm), nodular type, and CLN positivity are poor prognostic factors. A wide excision with close observation is advocated as the primary treatment for stage III LM. Adjuvant chemotherapy is useful for patients with stage IV cancer, but not for those with stage III.

Rapamycin inhibits Toll-like receptor 4-induced pro-oncogenic function in head and neck squamous cell carcinoma.

Toll-like receptor 4 (TLR4) is expressed in head and neck squamous cell carcinoma (HNSCC) cells and is associated with HNSCC cancer progression. Rapamycin has been proven to be efficient for the treatment of HNSCC in vivo, yet the mechanism is not understood and rapamycin demonstrates little effect in vitro. In the present study, the HNSCC cell lines CAL27 and SCC4 were pre-treated with rapamycin then stimulated with a TLR4 ligand lipopolysaccharide (LPS). Cell proliferation, migration, invasion, resistance to TRAIL-induced apoptosis, cytokine production, NF-κB and p65 activation were determined. The results indicated that LPS significantly stimulated HNSCC cell proliferation, cytokine production, migration, invasion and resistance to apoptosis induced by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). Pretreatment with rapamycin significantly attenuated LPS-induced pro-oncogenic effects by inhibiting the activation of NF-κB by LPS. siRNA knockdown of TLR4 in HNSCC cells demonstrated that rapamycin attenuated LPS-induced pro-oncogenic effects via TLR4. Hence, this study suggests rapamycin may be efficient for the treatment of HNSCC by attenuating TLR4-induced pro-oncogenic effects.

Sequential therapy of advanced buccal mucosa squamous cell carcinoma: three-year outcome.

PURPOSE: Squamous cell carcinoma (SCC) of the buccal mucosa is aggressive and requires multimodal treatment. The objective of this study was to evaluate the outcome of sequential therapy (neoadjuvant therapy plus surgery plus radiotherapy) in advanced buccal SCC and explore the prognostic factors. PATIENTS AND METHODS: In this retrospective cohort study, patients with advanced buccal cancer who received neoadjuvant chemotherapy (cisplatin, docetaxel, and 5-fluorouracil) followed by surgery and radiotherapy in the authors' department were reviewed. The outcomes of chemotherapy and surgery were analyzed. Overall survival (OS) and disease-free survival (DFS) were calculated using the Kaplan-Meier method. The prognostic values of age, gender, histologic grade, lymph node status, tumor stage, pathologic response, and adverse pathologic features were explored using the log-rank test and the Cox regression model. RESULTS: From 2008 to 2011, data from 22 patients were analyzed. The overall response rate of chemotherapy was 72.7%. The pathologic complete or partial response rate was 40.9%. The median follow-up was 36 months. The 2-year DFS and OS rates were 63.3% and 67.2%, respectively. Male and younger patients showed an association with poor outcome. Multivariate analysis showed that gender was a predictive factor with respect to DFS and OS (P = .023 and .014, respectively). CONCLUSION: Sequential therapy (neoadjuvant therapy plus surgery plus radiotherapy) tends to be effective for advanced buccal cancer. Female patients have better survival.